Sommer Ulrike, Morales Johanna, Groenewegen Andrea, Müller Annemarie, Naab Julia, Woerly Gaetane, Kamphausen Esther, Marsot Helene, Bennett Patrick, Kakkanaiah Vellalore, Vitaliti Alessandra
1Novartis Institutes for BioMedical Research, Basel, Switzerland.
2Biomarker Laboratories, PPD Inc., Richmond, VA 23230, USA.
Bioanalysis. 2015;7(10):1299-311. doi: 10.4155/bio.15.61.
Flow cytometry is increasingly becoming an important technology for biomarkers used in drug discovery and development. Within clinical development flow cytometry is used for the determination of PD biomarkers, disease or efficacy biomarkers or patient stratification biomarkers. Significant differences exist between flow cytometry methodology and other widely used technologies measuring soluble biomarkers including ligand binding and mass spectrometry. These differences include the very heavy reliance on aspects of sample processing techniques as well as sample stabilization to ensure viable samples. These differences also require exploration of new approaches and wider discussion regarding method validation requirements. This paper provides a review of the current challenges, solutions, regulatory environment and recommendations for the application of flow cytometry to measure biomarkers in clinical development.
流式细胞术日益成为药物研发中用于生物标志物的一项重要技术。在临床开发中，流式细胞术用于测定药效学生物标志物、疾病或疗效生物标志物或患者分层生物标志物。流式细胞术方法与其他广泛使用的测量可溶性生物标志物的技术（包括配体结合和质谱分析）之间存在显著差异。这些差异包括非常依赖样品处理技术的各个方面以及样品稳定化以确保样品的活性。这些差异还需要探索新方法并就方法验证要求进行更广泛的讨论。本文综述了当前在临床开发中应用流式细胞术测量生物标志物所面临的挑战、解决方案、监管环境及建议。
